Familial Hemophagocytic Lymphohistiocytosis With Heterozygous STX11 and Homozygous UNC13D Mutations Diagnosed in the Neonatal Period.

Patients with primary hemophagocytic lymphohistiocytosis may present with different mutations and phenotypic findings. It is usually presented as case reports because of its rare occurrence. Here, we discuss a case diagnosed with familial hemophagocytic lymphohistiocytosis 3, that presented in the neonatal period and was detected to have homozygous UNC13D and heterozygous STX11 mutations.

Low isolated ferritin levels without anemia: is gastrointestinal tract endoscopy sufficient to explain the cause?

AIM: The present study assesses the diagnostic significance of low ferritin levels in gastrointestinal diseases by evaluating the endoscopic findings of patients with low ferritin levels without anemia. METHOD: The study included patients aged 0-18 years who underwent an upper and lower gastrointestinal system endoscopy in the Pediatric Gastroenterology Department of our hospital. The patients were divided into three groups based on hemoglobin, and ferritin levels at the time of initial presentation and endoscopic and histopathological findings were recorded retrospectively. RESULTS: In the present study, 2391 pediatric patients were reviewed, among which 29% (n = 699) had anemia, 23% (n = 549) had low ferritin levels without anemia, and 48% (n = 1143) did not have anemia. The most common symptoms were abdominal pain, dyspepsia, and growth retardation. When the endoscopy findings were compared with those of patients with non-anemic group, Helicobacter pylori gastritis (24%/17.6%) and celiac disease (6%/2.2%) were more common in low ferritin levels without anemia, which indicated a statistically significant difference (p = 0.000/p = 0.04). CONCLUSIONS: Helicobacter pylori gastritis and celiac disease were more commonly observed in association with low ferritin levels. Low ferritin levels without anemia can be an early and silent sign of celiac disease.

Amitriptyline Intoxication in Children: Twenty Years' Experience in a Tertiary Care Center in Turkey.

BACKGROUND: Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages. METHODS: The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms. RESULTS: Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication. CONCLUSIONS: Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.

Chemotherapy-related fever or infection fever?

BACKGROUND: The present study investigates the reason for the onset of fever after chemotherapy (CT) for cancer with the aim of reducing unnecessary medical care. METHODS: A total of 37 consecutive cycles of CT for cancer were analyzed retrospectively from the files of patients. Fever was defined as a temperature of ≥ 38 °C lasting for 1 h. RESULTS: The study sample included 23 males and 14 females (aged 8.43 ± 5.04 [min-max]). Fever was observed in all 37 cycles of chemotherapy agent (CA), which included cytarabine (ARA-C), dacarbazine, cyclophosphamide, irinotecan, adriamycin, etoposide, ifosfamide, cisplatin, and methotrexate. Fever was recorded within the first 12 h following treatment with ARA-C (45.9%), dacarbazine (16.2%), or cyclophosphamide (8.1%). A physical examination of the patients yielded normal results, C-reactive protein (CRP) and procalcitonin (PCT) values were within the normal range, the median absolute neutrophil count (ANC) was 3200/uL (0.00-16.340/uL), and a median sedimentation (ESR) level of 10 mm/h (2-59) was determined. All fevers were accepted as having resulted from CT based on the above criteria. Paracetamol and diphenhydramine were administered and the patients' treatments were continued. CONCLUSION: Febrile episodes occurring within the first 6 h following treatment were considered to constitute an adverse drug reaction after CT for the treatment of cancer. While ARA-C fever has been previously reported on in the literature, it should be kept in mind that CT fever can be seen with different CA. Physicians should be aware of this aspect of chemotherapy-associated fever and avoid unnecessary examinations and treatments, including antibiotics.

Acquired noncaustic esophageal strictures in children.

BACKGROUND: Esophageal stricture (ES) is an uncommon clinic entity in pediatrics that may be congenital or acquired in childhood. Acquired noncaustic ES is very rare, and clinical features of affected patients are unknown. PURPOSE: We aimed to evaluate the clinical findings, and outcomes of patients with acquired noncaustic ES to aid physicians in the early referral of patients to gastroenterologists. METHODS: The medical data of patients with acquired noncaustic ES who were followed in our gastroenterology clinic between January 2009 and December 2019 were reviewed. RESULTS: Acquired noncaustic ES was found in 12 of the 4,950 patients (0.24%) who underwent endoscopy during the study period. The main symptoms were dysphagia (58.3%), vomiting (33.3%), and chronic anemia (8.3%). Chronic malnutrition and underweight were found in 66.6% of the patients. The most common etiological factors were radiotherapy, peptic reflux, and achalasia (16.6%, each), while chemotherapy, squamous-cell carcinoma (SC) of the esophagus, eosinophilic esophagitis (EoE), esophageal web, epidermolysis bullosa, and esophageal diverticulum (8.2%, each) were the other etiological factors. Patients with EoE underwent endoscopic bougie dilation in addition to steroid use and elimination diet. Patients with epidermolysis bullosa and esophageal web underwent bougie dilation. Patients with peptic reflux-related ES were initially put on antireflux therapy, but during follow-up, one patient required esophageal replacement with colonic interposition. Patients with radiotherapy-related ES recovered with medical therapy. The patient with initially underwent surgical gastrostomy and tumoral mass excision. The patient then received chemotherapy and radiotherapy and underwent jejunal interposition. Patients with achalasia underwent surgical esophagomyotomy. CONCLUSION: The presence of solid dysphagia, malnutrition, and an associated disease may alert physicians to the presence of ES.

Therapeutic effect of N-acetylcysteine on chemotherapy-induced liver injury.

BACKGROUND: N-acetylcysteine (NAC) may be useful in the management of chemotherapy-induced liver injury. AIMS: The present study evaluates the possible therapeutic effects of NAC on chemotherapy-induced hepatotoxicity. METHODS: A total of 102 patients' files who were diagnosed with cancer between 2015 and 2019 were evaluated retrospectively. Two patient groups with and without NAC were selected. NAC was administered in a 3-µg/kg IV dose in a 24-h infusion to 70 patients when any alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) values reached three times the normal levels. The other group consisted of 32 patients who were not treated with NAC. Alanine aminotransferase and GGT values were recorded at pretreatment, and on the 1st, 3rd, 5th, and 7th days in both the NAC and non-NAC groups from files. RESULTS: In the NAC group, ALT and GGT values on day 1, 3, 5, and 7 differed from each other, decreasing from day 1 to day 7. A statistically significant difference was noted between the values in the NAC group (p < 0.001). In the non-NAC group, the ALT values on day 7 were lower than the ALT values on day 1. A comparison of the ALT and GGT values in the NAC and non-NAC groups found that the values in the NAC group decreased earlier than in the non-NAC group. CONCLUSIONS: This study shows that NAC has a therapeutic effect on hepatotoxicity in children being treated with chemotherapeutic agents due to underlying malign diseases. The early reduction in the results of liver function tests is important for the continuation of chemotherapy.

Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children with Immune Thrombocytopenia in Turkey

Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children. Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia. Results: The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients. Conclusion: Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.

Bladder Artery Embolization for Massive Hematuria Treatment in a Patient With Ataxia-Telangiectasia Acute Lymphoblastic Leukemia.

Ataxia-telangiectasia (AT) is a hereditary recessive autosomal disorder following a course of progressive cerebellar ataxia, and oculocutaneous telangiectasia. Disease-specific telangiectasias are generally localized in the oculocutaneous region, while telangiectasias located within the bladder are rarely seen in patients with AT. The patient who had been followed-up with a diagnosis of AT since the age of 3 years was later diagnosed with acute lymphoblastic leukemia at the age of 8 years. The patient developed hematuria approximately in the 29th month of treatment. The cystoscopy revealed regions of extensive hemorrhagic telangiectasis, which was interpreted as the bladder involvement of AT. The case presented here underwent several cycles of intravesical steroid and tranexamic acid treatments and intravesical cauterization procedures, but the patient was unresponsive to all medical treatment approaches. The patient was consequently evaluated by an interventional radiology unit for a selective arterial embolization. The patient's hematuria resolved after embolization. Bladder wall telangiectasia may, on rare occasions, develop in patients with AT, and can result in life-threatening hemorrhages. We also suggest that a selective arterial embolectomy can be safely carried out in pediatric patients with treatment-resistant intravesical bleeding.

Constitutional Mismatch Repair Gene Defect Syndrome Presenting With Adenomatous Polyposis and Cafe au Lait Spots: A Case Report.

INTRODUCTION: Adenomatous polyps in the gastrointestinal system rarely occur in childhood and are accompanied by syndromes such as Familial adenomatous polyposis, attenuated familial adenomatous polyposis, and MUTYH-associated polyposis, Gardner and Turcot syndrome, and also mismatch repair (MMR) gene defects. In this article, we want to present a rare patient who had adenomatous polyposis and in situ carcinoma and was detected biallelic MMR gene defect. CASE: A 16-year-old female patient admitted with painless rectal bleeding, chronic abdominal pain, and anorexia for 1 year. Her physical examination was notable for multiple cafe au lait spots. The colonoscopic and histopathologic examination revealed multiple adenomatous polyps that one of them contains low-high grade dysplasia and in situ carsinoma. Genetic analysis revealed a homozygous mutation in the PMS2 gene [c.1164delT (p.H388Qfs*10) (p.His388GInfsTer10)] and she was diagnosed with constitutional MMR gene defect syndrome. Polypectomy was performed 4 times in 2 years period. Then, the patient's last colonoscopic examination revealed a large broad polyp in the rectum and multiple polyps in the other colon segments, and she underwent colectomy because of high risk of colorectal cancer. CONCLUSIONS: Adenomatous polyps are very important in childhood because of rarity. In particular, the presence of cafe au lait spots and a history of malignancy detected in relatives at an early age must be considered for CMMRD.

Augmented mitochondrial cytochrome c oxidase activity in children with iron deficiency: a tandem between iron and copper?

INTRODUCTION: Dyshomeostasis of essential trace elements including iron and copper plays a key role in the pathogenesis of a myriad of serious conditions including iron deficiency (ID) anemia, in which impaired cellular energy metabolism is prominent. Although experimental studies documented decreased activity of cytochrome c oxidase (CytOx) in ID, there are not enough clinical data. The present study was conducted to determine serum copper levels and activity of mitochondrial CytOx in isolated lymphocytes of patients with iron deficiency. MATERIAL AND METHODS: A total of 210 cases (2-17 years) were included in this prospective study. Serum iron and copper levels were measured. According to the serum iron levels, patients were allocated to iron deficient (ID, n = 70) and iron deficiency anemia (IDA, n = 70) groups, and iron-sufficient participants were allocated to the control group (n = 70). Activity of CytOx in the circulating lymphocytes was colorimetrically measured and compared with the controls. RESULTS: The CytOx activity was significantly higher in the IDA (2.9 ±1.2 mOD/min, n = 62) group compared to the control group (2.4 ±1.3 mOD/min, n = 68, p < 0.001). Interestingly, serum copper levels were significantly higher in both the ID (106.9 ±55.5 µg/dl, n = 64, p = 0.0001) and IDA (115.1 ±50.2 µg/dl, n = 59, p = 0.0001) groups than the control group (72.1 ±46.7 µg/dl, n = 69). CONCLUSIONS: Higher serum copper levels in patients with IDA implicate co-operative interaction between these trace elements. The elevated CytOx activity in patients with IDA is probably secondary to the normal/elevated serum copper levels.

Juvenile Myelomonocytic Leukemia in Turkey: A Retrospective Analysis of Sixty-five Patients.

OBJECTIVE: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies. MATERIALS AND METHODS: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey. RESULTS: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time. CONCLUSION: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

A Case of ALL Developing Posterior Reversible Encephalopathy Secondary to Hyponatremia.

Posterior reversible encephalopathy syndrome (PRES), may be due to different causes. It may develop secondary to hypertension, renal decompensation, electrolyte imbalance, and chemotherapeutic drugs. We describe a case of acute lymphoblastic leukemia in which PRES developed secondary to hyponatremia despite being normotensive during receipt of chemotherapy. Magnetic resonance imaging findings were suggestive of PRES. Partial diffusion restriction was observed in lesions in the bilateral occipitoparietal regions and the cerebellum. The patient was treated with appropriate medications with the resolution of his stroke-like symptoms. No neurological deficit was observed and clinical condition improved. The patient continued with chemotherapy. Early diagnosis and treatment of this syndrome is important in terms of preventing neurological sequelae. Cases of secondary PRES developing for several etiological reasons have been reported in induction therapy, but no pediatric cases of PRES developing secondary to hyponatremia despite being normotensive while receiving chemotherapy in acute lymphoblastic leukemia have previously been reported.

ARC syndrome.

Mutlu M, Aslan Y, Aktürk-Acar F, Çakir M, Erduran E, Kalyoncu M. ARC syndrome. Turk J Pediatr 2017; 59: 487-490. Arthrogryposis-renal dysfunction-cholestasis (ARC) is an autosomal recessive multisystem disorder characterized by arthrogryposis, renal tubular dysfunction and neonatal cholestasis with low gamma glutamyl transpeptidase activity. Most of the mutations in ARC syndrome are associated with the vacuolar protein sorting 33B (VPS33B) gene on chromosome 15q26.1. Herein, we report a female newborn with ARC syndrome caused by homozygous mutations in VPS33B [IVS1-2A > C (c.97-2A > C)].

Diffuse Adenomyomatosis of the Gallbladder in a Child.

Adenomyomatosis of the gallbladder (ADMG) is characterized by proliferation of the mucosal epithelium and hypertrophy of the muscularis. ADMG is predominantly diagnosed by using ultrasonography. Although ADMG is benign in nature, lithiasis, and chronic inflammation secondary to it may lead to dysplastic changes and cancer. Mucosal invagination through the hypertrophied muscularis results in large intramural diverticula or sinus tracts which are visible at radiology, known as Rokitansky-Aschoff sinuses. Histologically, ADMG manifests with hyperplasia of the muscular layer and proliferation of mucosal glandular tissues. We describe a case of ADMG in an 8-year-old girl presenting with recurrent abdominal pain. Diagnosis was made using ultrasound, and the condition was successfully treated with open cholecystectomy. Ultrasound scanning in children presenting with recurrent abdominal pain may lead to more accurate diagnosis of ADMG during childhood.

Positive correlation between insulin resistance and iron overload-induced oxidative stress in patients with fanconi anemia (FA)- and non-FA-related bone marrow failure: The results of a multicenter study.

This study investigated the relationship between DNA, protein, and lipid oxidations and insulin resistance in patients with Fanconi anemia (FA)- and non-FA-related bone marrow failure. Sixteen patients with FA, 7 non-FA-related aplastic anemia, and 10 controls were included in the study. Fasting blood glucose, simultaneous insulin, hepcidin, ferritin, 8-hydroxy deoxyguanosine (8-OHdG), protein carbonyls, malondialdehyde (MDA), and homeostatic model assessment-insulin resistance (HOMA-IR) were investigated in the patients and controls. Diepoxybutane test-positive (DEB+) patients were diagnosed with FA, whereas DEB-patients were diagnosed as non-FA. 8-OHdG levels in both FA and non-FA patients were significantly higher than those in the controls (P = .001 and P = .005, respectively). Serum ferritin levels were also higher in FA and non-FA patients than in the controls (P = .0001 and P = .005, respectively). Insulin resistance (IR) was significantly higher in FA patients than in non-FA patients and controls (P = .005 and P = .015, respectively). Significant differences were observed between 8-OHdG, ferritin, and MDA levels in patients with or without IR (P = .009, P = .001, and P = .013, respectively). Moderate and strong relations of 44% and 85% were determined between IR and ferritin levels in patients with FA or non-FA (P = .08 and P = .014, respectively). FA and non-FA patients exhibited a tendency to IR. IR was related to ferritin levels, and ferritin levels were also correlated with oxidative stress. These findings suggest that the increased rate of IR in patients with FA and non-FA may derive from increased oxidative stress, which may in turn be due to elevated serum ferritin levels.

A newborn with trisomy 13 presenting with cloacal exstrophy.

Trisomy 13 syndrome is a rare disorder that carries a high mortality rate due to abnormal prenatal development resulting in serious birth defects. Although genitourinary malformations are commonly seen in trisomy 13 syndrome, to our knowledge, the association of cloacal exstrophy with trisomy 13 has been extremely rarely reported. Herein, a newborn with trisomy 13 syndrome having multiple congenital anomalies, including cloacal exstrophy, is presented, and the importance of structural anomalies of the neutrophilic leukocytes on a blood smear in supporting diagnosis of trisomy 13 is discussed.

Hepcidin levels in children with chronic liver disease.

BACKGROUND/AIM: We aimed to analyze serum hepcidin level in children with chronic liver disease (CLD) and its relationship with serum cytokines level, liver function tests, hepatic iron content, and liver fibrosis. PATIENTS AND METHODS: The study included 34 children with CLD, and 15 age- and gender-matched healthy children. Serum hepcidin, ferritin, iron level, interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß ), total oxidant status (TOS), and antioxidant status (TAS) were studied in all patients and in the control group. Liver iron content (LIC) was measured from the liver biopsy specimen. RESULTS: Serum ferritin levels were higher in patients with CLD than control group (100.1 ± 98.2 ng/mL vs 50.5 ± 32.2 ng/mL, P = 0.016). No significant difference was found in hepcidin levels. Hepcidin levels in children with CLD was positively correlated with ferritin (r = 0.75, P = 0.001), pediatric end-stage liver disease (PELD) score (r = 0.56, P = 0.001), TAS (r = 0.42,P = 0.02), but negatively correlated with albumin level (r = -0.45,P = 0.008). Transferrin saturation and hepcidin:ferritin ratio were significantly low in patients with severe fibrosis compared with patients with mild/without fibrosis (15.5 ± 5.5 vs 34.3 ± 30.1, P = 0.017 and 1 ± 0.5 vs 1.9 ± 1.4,P = 0.04, respectively). CONCLUSION: Serum hepcidin levels in children with CLD reflect both liver functions and TAS, and severe fibrosis is associated with low hepcidin:ferritin ratio in children with CLD.